Gene expression profiling reveals the plausible mechanisms underlying the antitumor and antimetastasis effects of Andrographis paniculata in esophageal cancer

Abstract

Esophageal cancer (EC) is a seriously invasive malignancy with high mortality and poor prognosis. Metastasis of EC is the major cause of mortality. Our studies previously demonstrated that a herbal medicine Andrographis paniculata (AP) significantly suppressed EC growth and metastasis in vitro and in vivo. However, the underlying mechanisms responsible for these effects have not yet been systematically elucidated. In this context, gene expression profiling of AP-treated squamous EC cells (EC-109) was performed to reveal the regulatory mechanisms of AP in antitumor and antimetastasis signaling pathways using gene expression microarray analysis. Differentially expressed genes were identified by Affymetrix Gene Chip, followed by the real-time polymerase chain reaction validation. The results showed that the canonical pathways were significantly regulated by AP treatment, including multiple genes related to proliferation, apoptosis, intercellular adhesion, metastatic processes, and drug resistance, such as WNT, TGF-β, MAPK and ErbB signaling pathways, and ATP-binding cassette transporter subfamily members. This genomic study emerges candidate molecular targets and pathways to reveal the mechanisms involved in AP's effects, which provides scientific evidence to support the clinical application of AP in EC treatment.

Network pharmacology reveals potential functional components and underlying molecular mechanisms of Andrographis paniculata in esophageal cancer treatment

“…Knockdown of EGFR suppresses the proliferation, migration and invasion of ESCC cells, and increases the percentage of G1 phase cells (Zeng et al, 2019). In fact, EGFR is one of the genes identified in our previous microarray‐based gene profiling study on the antitumor/antimetastatic effects of AP on EC (Li et al, 2018). STAT3 is a transcription factor downstream of EGFR, whose constitutive activation can promote oncogenesis.…”

“…APW downregulates the gene and protein expression of metastasis‐related factors such as transmembrane 4 superfamily member 3 (TM4SF3), human epidermal growth factor receptor 2 (HER2), and chemokine (C‐X‐C motif) receptor 4 (CXCR4; Li et al, 2017; Yue et al, 2015) in EC‐109 cells. It also reduces the expression of genes related to cell growth, differentiation, migration, and proliferation, including epidermal growth factor receptor (EGFR), platelet‐derived growth factor receptor beta (PDGFRB), and the transmembrane protein KIAA1109, in the same cell line (Li et al, 2018). Moreover, we have recently shown that the antimetastatic efficacy of APW on liver metastasis of EC in xenograft‐bearing mice relies, at least partly, on the gut microbiota (Cheung et al, 2020).…”

Study on the Antitumor Effect and Glycolysis of Andrographolide in Anaplastic Thyroid Carcinoma

“…Furthermore, it has been studied that andrographolide-induced cell proliferation decrease may be attributed to the inhibition of fatty acid synthesis, iron uptake, protein synthesis, and FLT3 signaling in MV4-11 cells [18]. In esophageal cancer, Andrographis paniculata has also been reported to exert an antitumor effect and is related to multiple signaling pathways including WNT, TGF-β, MAPK, and ErbB pathways [19]. In addition, some studies have found that andrographolide has obvious inhibitory effects on lung, liver, gastric, esophageal, and breast cancers, among others [20], showing good antitumor activity of andrographolide.…”

An innovative anti-cancer Chinese herbal formula exhibited multi-targeted efficacies in metastatic breast cancer mouse model

“…Among these herbs, Andrographis paniculata (AP, 穿心蓮), Acanthopanax senticosus (AS, 刺五加), Camellia sinensis (CS, 綠茶), and Hedyotis diffusa (HD, 白花蛇舌草) were shown to have promising anti-cancer-related bioactivities. Aqueous extract of AP has been shown to potently inhibit tumor growth and metastasis in esophageal cancer mice in our previous studies [14–16]. Acanthopanax senticosus (AS) was investigated for its anti-tumor and immunomodulatory activities in breast cancer cells and immuno-competent mice models [17], unpublished data].…”